Abstract Summary While all implants have capacity for generation of post-surgical adhesions, there is an estimated incidence rate as high a 58%, of adhesions which are so prohibitive that further intervention is warranted. Classical approaches of using polymer meshes or mesh coatings have not been universally adopted due to high cost, poor mesh mechanics, or capacity for immune activation and further amplification of chronic inflammation. Anti-adhesive surfaces such as the endothelial glycocalyx are formed by cell surface oligo- and polysaccharides, which are simple to reproduce and non-immunogenic. Therefore, we propose to create a family of polysaccharide-based polymers to coat hernia repair meshes mimicking the anti- adhesive properties of the glycocalyx. Preliminary data both in vitro and in rodent and pig models have shown this strategy to reduce adhesions beyond that of uncoated meshes. Our long-term goal is to develop a low-cost, biocompatible device coating which can prevent or reduce post-surgical adhesions. The objective of this proposal is to assess the range of polysaccharide chemistries capable of preventing adhesions, while retaining mesh repair durability and biocompatibility. The central hypothesis is that polysaccharide-based polymers, due to their capacity to form a water shell will resist protein adsorption and cell adhesion, reducing the number of post-surgical adhesions. This work will be accomplished in three aims: 1) Validate the capacity to prevent protein and cell adhesion on hernia meshes. 2) Evaluate impact of coating on post-surgical adhesion and durability of hernia repair. 3) Examine biocompatibility of polymer coatings in our rodent model. Our proposed work is innovative; it mimics simple saccharide chemistries to reduce adhesions; and by using naturally-derived molecules has a higher likelihood of biocompatibility. The expected outcomes include a platform technology, broadly applicable for use in reducing post-surgical adhesions. These results will positively impact the field of general surgery by providing a solution to a vexing problem that has complicated surgical care since meshes were introduced nearly 50 years ago. Future work will further assess biocompatibility at a molecular level, and translate to a large animal model of hernia repair and post-surgical adhesion.